Membrane cation transport, membrane permeability and cell membrane potential are in a dynamic state throughout the cell cycle. Certain of these properties differ in normal versus malignant cells. However, no direct comparison of all of these membrane ionic properties has been made in a single cell line and its transformed counterpart. As a result, the functional significance of these membrane properties and their relationship to the onset and maintenance of the malignant state are unknown. Cellular levels of cyclic AMP also change during the cell cycle and there is evidence implicating cAMP in control of the mammalian cell cycle. We propose first, to establish the nature of cation flux, cation permeability and the cell membrane potential at each stage of the cell cycle in synchronously growing normal and transformed BHK cells (BHK 21 and PyBHK H3 respectively). These will be established by electrophysiological measurements and isotope flux analysis, both of which the BHK cell is suitable for. Secondly, we shall determine levels of cAMP at each stage of the cell cycle in the normal and transformed cell using an isotope dilution technique. From this data, temporal relationships between cAMP and the membrane properties will be established. Based on these observations we then propose to investigate causal relationships between these parameters. These experiments will involve experimental manipulation of cellular cAMP, transport, permeability and membrane potential at specific stages of the cell cycle. This data will establish whether certain membrane properties are required for maintenance of cAMP levels or, conversely, whether cAMP levels regulate any or all of the membrane properties or if there is no direct relationship between these events. We shall be particularly interested in any causal relationship which exist in terms of a comparison of these in the normal versus transformed cell. Factors which regulate the membrane properties in question may in turn be integral in the membrane associated events of adhesion, contact inhibition and metabolite transport. In turn, any membrane properties which regulate cellular cAMP may be integral in control of the cell cycle.